chrX-48791112-G-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_002049.4(GATA1):c.3G>T(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 22)
Consequence
GATA1
NM_002049.4 start_lost
NM_002049.4 start_lost
Scores
6
5
3
Clinical Significance
Conservation
PhyloP100: 3.79
Genes affected
GATA1 (HGNC:4170): (GATA binding protein 1) This gene encodes a protein which belongs to the GATA family of transcription factors. The protein plays an important role in erythroid development by regulating the switch of fetal hemoglobin to adult hemoglobin. Mutations in this gene have been associated with X-linked dyserythropoietic anemia and thrombocytopenia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_002049.4 (GATA1) was described as [Pathogenic] in ClinVar as 156265
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-48791112-G-T is Pathogenic according to our data. Variant chrX-48791112-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 1068653.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA1 | NM_002049.4 | c.3G>T | p.Met1? | start_lost | 2/6 | ENST00000376670.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA1 | ENST00000376670.9 | c.3G>T | p.Met1? | start_lost | 2/6 | 1 | NM_002049.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Diamond-Blackfan anemia;C1845837:GATA binding protein 1 related thrombocytopenia with dyserythropoiesis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 11, 2020 | For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been reported to affect GATA1 protein function (PMID: 20729467, 24952648). Disruption of the initiator codon has been observed in individual(s) with Diamond-Blackfan anemia (PMID: 24453067, 24952648, 29146883). This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the GATA1 mRNA. The next in-frame methionine is located at codon 84. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
B;.
Vest4
MutPred
Gain of catalytic residue at M1 (P = 0.0919);Gain of catalytic residue at M1 (P = 0.0919);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.